Thirteen patients with schizophrenia received injections of 25, 50, or 75 mg of long-acting risperidone every 2 wk. Brain D2 receptor occupancy was assessed with [C-11]raclopride 2 wk after the last (fifth) injection (day 71) in seven subjects and 2 wk after the third injection (day 44) in one subject. Stable plasma concentrations were reached after the third injection and steady-state concentrations of the active moiety (risperidone +9-hydroxyrisperidone) after the fourth injection. Steady-state plasma concentrations were maintained for 4-5 wk after the last injection and then declined rapidly. After injections of 25, 50 and 75 mg on day 44 or day 71, D2 receptor occupancy ranged from 25-48%,59-83% and 62-72% respectively, while plasma active-moiety levels ranged from 4.4-8.8, 15.0-31.1 and 22.5-26.3 ng/ml respectively. The results indicate that brain D2 receptor occupancy at steady state after injections of long-acting risperidone was in the range found in patients effectively treated with 2-6 mg; of oral risperidone.

Positron emission tomography (PET) has been shown to be of great importance in elucidating the mechanism of action of antipsychotic drugs. In psychotic patients L-[11C]DOPA PET has been used to demonstrate some differences in dopaminergic activity compared with that in healthy volunteers. Ten healthy volunteers were investigated with PET and L-[11C]DOPA. Ten drug-free patients with psychosis, nine stable schizophrenics treated with clozapine, and nine stable patients treated with classical antipsychotics were also investigated with L-[11C]DOPA. Principal-component analysis was employed for the analysis of L-[11C]DOPA Ki values across a number of corticostriatal brain regions. These data revealed a significant three-component model with clear-cut separation between healthy controls and patients with unmedicated schizophrenia. Stable optimal treatment with either classical neuroleptics or clozapine partially, albeit differentially, reversed the aberrant patterns seen in drug-free schizophrenia. It can thus be concluded that schizophrenia is associated with abnormal patterns of L-[11C]DOPA utilization in corticostriatal systems. Treatment with clozapine or classical neuroleptics induces partial, albeit differential, normalization of the abnormal patterns seen in untreated schizophrenia.

The postoperative development or worsening of gastroesophageal reflux disease (GERD) represents the major drawback of laparoscopic sleeve gastrectomy (SG). A GERD diagnosis is often based only on symptoms and proton pump inhibitors (PPI) intake, while objective tests like esophagogastroduodenoscopy and pH measurements are performed less frequently.To evaluate the association between reflux symptoms and GERD-related esophageal lesions.University hospital, Rome, Italy.A comprehensive clinical control entailing GERD symptoms, PPI intake, and esophagogastroduodenoscopy was proposed to all patients who underwent SG between June 2007 and February 2011, irrespective of the presence of GERD symptoms. One hundred forty-four of 219 patients agreed to take part in the study (follow-up rate: 65.8%).After a mean follow-up of 66 months, GERD symptoms and PPI intake were recorded in 70.2% and 63.9% of patients, respectively. Mean visual analogue scale score was 2.9 ± 3.3. The overall frequency of erosive esophagitis was 59.8%, while nondysplastic Barrett's esophagus was detected in 13.1%. The frequency of esophageal biliary reflux was 68%. GERD symptoms and visual analogue scale score were not significantly associated with the development of erosive esophagitis and Barrett's esophagus and the severity of the esophageal lesions. Moreover, the frequency of erosive esophagitis and Barrett's esophagus in patients consuming PPI were similar to that of patients without PPI.Symptoms investigation alone is not a reliable tool to diagnose GERD after SG. The use of objective diagnostic tests, such as esophagogastroduodenoscopy, should be carefully considered in the postoperative follow-up schedule of SG patients.

Objective: Quetiapine is a novel antipsychotic agent with many atypical features, including low D-2 and higher 5HT(2A) affinity in vitro, low propensity to induce extra-pyramidal side effects and minimal effects on prolactin levels. The purpose of this study was to investigate, using position emission tomography (PET), the relationship between plasma concentrations of different doses of quetiapine and occupancy of D-2 and 5HT(2A) receptors in schizophrenic patients, Methods: Five patients were treated with quetiapine (titrated to 750 or 450 mg/day) for 28 days, subsequently reduced weekly in a descending-dose schedule. Dopamine D-2 and 5HT(2A) occupancies were determined using [C-11] raclopride and [C-11] N-methylspiperone as ligands, respectively, and PET imaging. Results: Mean D, receptor occupancies of 41 and 30%, were observed at quetiapine doses of 750 and 450 mg/day. At lower dose levels no occupancy could be determined. Quetiapine: induced a consistently higher degree of 5HT(2A) receptor occupancy, with mean occupancies of 74 and 57% at doses of 750 anti 450 mg/day, respectively. No EPS emerged during the trial and most of the pre-trial EPS resolved during the study. Conclusions: In clinically effective doses, quetiapine induced low occupancy at D-2 receptors, which is consistent with atypical antipsychotics such as clozapine. and probably explains the lack of EPS observed in this trial. Correlations between receptor occupancy and plasma concentrations of quetiapine could not he calculated, although receptor occupancy increased with higher plasma concentrations for the 450 and 750 mg doses. (C) 2001 Elsevier Science B.V. All rights reserved.

Background: The aim of the present study was to investigate dopamine synthesis in the brain of drug-free schizophrenic patients, not only in the striatum but also in extrastriatal areas like the prefrontal cortex, brain areas that for a long time has been in focus of interest in the pathophysiology of schizophrenia.Methods: PET was performed in 12 drug;free (10 drug-naive) psychotic schizophrenic patients and 10 healthy volunteers matched for age and gender using (11)C-labelled L-DOPA as the tracer The time-radioactivity curve from occipital cortex (located within Brodman area 17 and 18) was used as input function to calculate L-DOPA influx rate, K(i) images, that were matched to a common brain atlas. A significant overall increase of the K(i) values was found in the schizophrenic group as compared with healthy controls.Results: In particular, significantly higher K(i) were found in the schizophrenic patients compared to the controls in the caudate nucleus, putamen and in parts of medial prefrontal cortex (Brod 24). The K(i) value reflect an increased utilization of L-DOPA, presumably due to increased activity of the amino acid decarboxylate enzyme.Conclusions: The results indicate that the synthesis of dopamine is elevated within the striatum and parts of medial prefrontal cortex in schizophrenia. Biol Psychiatry 1999;46:681-688 (C) 1999 Society of Biological Psychiatry.

A sensitive and specific HPLC assay for the measurement of the antipsychotic compound quetiapine in human plasma has been developed and validated. The assay employs a three-step liquid liquid extraction of quetiapine and its 7-hydroxylated and 7-hydroxylated, N-dealkylated metabolites from human plasma, and utilizes ultraviolet (UV) detection of quetiapine and electrochemical detection of the metabolites. The method provides a linear response from a quantitation limit of 2.50 to 500 ng ml(-1) for each analyte using 0.4 ml plasma. The assay is applicable from 500 to 5000 ng ml(-1) by sample dilution with de-ionized water. The inter-assay precision of quetiapine in plasma calibration standards across 4 validation days averaged 11.9% relative standard deviation (RSD) over the range 2.50 to 500 ng ml(-1), with intra-assay precision averaging 16.0% RSD and mean accuracy of 98.6% of theory. Similarly, the inter-assay precision of the 7-hydroxylated metabolite in plasma calibration standards across 4 validation days averaged 13.7% RSD over the range 2.50 to 500 ng ml(-1), with intra-assay precision averaging 17.6% RSD and mean accuracy of 109% of theory. The 7-hydroxylated, N-dealkylated metabolite demonstrated inter-assay precision of 16.2% RSD, intra-assay precision of 19.9% RSD, and mean accuracy of 104% of theory over the range 2.50 to 500 ng ml(-1). The present assay method was used to support a study comparing the pharmacokinetic profile of quetiapine with the time course of dopamine D2 and serotonin 5-HT2 receptor occupancy in the brain using positron emission tomography (PET). We describe in this paper the bioanalytical method and the plasma concentrations of quetiapine and its metabolites resulting from this study.